Liquid sulfur as a reagent: Synthesis of polysulfanes with 20 or more sulfur atoms with characterization by UPLC-(Ag+)-coordination ion spray-MS

Article abstract of DOI:10.1080/17415993.2012.721368

Diallyl disulfide reacts within minutes with liquid sulfur at 120°C giving a family of diallyl polysulfanes, All2S n (n=3-22), characterized by ultra-performance liquid chromatography-(Ag⁺)-coordination ion spray-mass spectrometry (UPLC-(Ag⁺)CIS-MS). Similarly, garlic oil (GO), bis-(2-methyl-2-propenyl), bis-(2-chloro-2-propenyl), bis-(3-methyl-2- butenyl), and bis-(2-cyclohexen-1-yl) disulfides all give families of polysulfanes with up to 22 sequential sulfur atoms. New members of families of silver chelators with up to 10 sulfur atoms were found in GO using UPLC-(Ag ⁺)CIS-MS. 2013 Copyright Taylor and Francis Group, LLC.

Full text of DOI:10.1080/17415993.2012.721368

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Liquid sulfur as a reagent: synthesis
of polysulfanes with 20 or more sulfur
atoms with characterization by UPLC-
(Ag+)-coordination ion spray-MS
Kai Wang a , Murree Groom b , Robert Sheridan c , Shaozhong Zhang
a & Eric Block a
a Department of Chemistry, University at Albany, SUNY, Albany, NY,
12222, USA
b ECOspray Limited, Grange Farm, Hilborough, Norfolk, IP26 5BT,
UK
c NYS Department of Agriculture and Markets, Food Laboratory
Division, Albany, NY, 12235, USA
Published online: 18 Sep 2012.
To cite this article: Kai Wang , Murree Groom , Robert Sheridan , Shaozhong Zhang & Eric Block
(2013) Liquid sulfur as a reagent: synthesis of polysulfanes with 20 or more sulfur atoms with
characterization by UPLC-(Ag+)-coordination ion spray-MS, Journal of Sulfur Chemistry, 34:1-2,
55-66, DOI: 10.1080/17415993.2012.721368
To link to this article: http://dx.doi.org/10.1080/17415993.2012.721368
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Journal of Sulfur Chemistry, 2013
Vol. 34, Nos. 1–2, 55–66, http://dx.doi.org/10.1080/17415993.2012.721368
Liquid sulfur as a reagent: synthesis of polysulfanes with
20 or more sulfur atoms with characterization by
UPLC-(Ag+)-coordination ion spray-MS
Kai Wanga, Murree Groomb, Robert Sheridanc, Shaozhong Zhanga and Eric Blocka*
aDepartment of Chemistry, University at Albany, SUNY, Albany, NY 12222, USA; bECOspray Limited,
c
Grange Farm, Hilborough, Norfolk IP26 5BT, UK; NYS Department of Agriculture and Markets, Food
Laboratory Division, Albany, NY 12235, USA
(Received 26 July 2012; final version received 13 August 2012)
Diallyl disulfide reacts within minutes with liquid sulfur at 120◦C giving a family of diallyl polysulfanes,
All2Sn (n = 3–22), characterized by ultra-performance liquid chromatography-(Ag+)-coordination ion
spray-mass spectrometry (UPLC-(Ag+)CIS-MS). Similarly, garlic oil (GO), bis-(2-methyl-2-propenyl),
bis-(2-chloro-2-propenyl), bis-(3-methyl-2-butenyl), and bis-(2-cyclohexen-1-yl) disulfides all give fam-
ilies of polysulfanes with up to 22 sequential sulfur atoms. New members of families of silver chelators
with up to 10 sulfur atoms were found in GO using UPLC-(Ag+)CIS-MS.
Keywords: elemental sulfur; UPLC-CIS-MS; diallyl polysulfides; garlic oil; thiosulfoxide
1. Introduction
While liquid sulfur occurs naturally (1) and is produced worldwide in excess of 35 × 106 tons/year
by the Frasch and Claus processes (2), surprisingly little work has appeared on its use as a reagent
for synthesis of monomeric organosulfur compounds (or other compounds) under mild condi-
tions (3–6). At 120◦C sulfur melts to a honey-yellow, low-viscosity liquid consisting of >95% S8
and remains liquid down to its triple point of 115◦C. In liquid form, sulfur is transported worldwide
by ship, rail, and heated pipeline (2). We examined the use of liquid sulfur, without added solvents
or catalysts, in transforming diallyl disulfide (1a; Scheme 1) into a mixture of higher linear poly-
=
sulfanes (CH2 CHCH2)2Sn (2a). This method was applied to diallylic disulfides 1b–1e and to
garlic oil (GO), containing 1a as a major component. Polysulfanes 2 are of interest in our Allium
chemistry research (7), particularly for use as environmentally benign nematicides (portions of the
*Corresponding author. Email: eblock@albany.edu
© 2013 Taylor & Francis

56 K. Wang et al.
material covered in this paper are the subject of patents based on joint discoveries made by E.B.
and M.G. at ECOspray Ltd in the UK: (7a) and earlier filings cited therein) (7b) and bird repel-
lants (7c). While polysulfane biological activity increases with the number of sulfur atoms (8),
diallylic polysulfanes with nine or more sulfur atoms are currently unavailable. We describe here a
simple approach, using liquid sulfur as a reagent, to the synthesis of families of allylic and diallylic
polysulfanes containing chains of up to 22 sulfur atoms, unavailable by other means (5) (polysul-
fane synthesis: with S8 and Rh catalyst (9a), with methyl triflate (9b), and from sulfenyl halides
(9c)). We also describe the use of ultra-performance liquid chromatography-(Ag+)-coordination
ion spray-mass spectrometry (UPLC-[Ag+]CIS-MS) to characterize the complex mixtures of
sulfur compounds involved in this work, including those in GO.
Scheme 1. Diallylic polysulfane synthesis.
2. Results and discussion
Diallyl disulfide (1a) and molten S8 in a 1:1 molar ratio (calculated for sulfur as S8) was stirred
at 120◦C. The initially heterogeneous mixture became homogeneous within 3 min (Figure 1).
C18-HPLC analysis of reaction mixtures showed a series of evenly spaced peaks, eluting over
=
the course of 3 h, corresponding to (CH2 CHCH2)2Sn (2a), n = 3–22, along with unreacted
S8. The reaction was terminated after 1 h (Figure 2), after which time darkening occurred.
Diode array UV spectra of each peak supported the “family” relationship of members of the
mixture (see Supporting Information). Prior HPLC studies of dialkyl polysulfanes revealed lin-
ear relationships between the number of sulfur atoms in the chain and the natural logarithm
of the capacity factor, calculated from the retention time (5, 10). Similar linear relationships
for the relative UV detector response (e.g. higher sensitivity to higher polysulfanes) were also
found (9b).
While mixtures of 2a can be characterized by 1H NMR spectroscopy, since the SCH2 signal
moves downfield as the number of sulfur atoms increase, for example, δ 3.11, 3.36, 3.52, 3.60, and
3.63, for 2a, n = 1–5, respectively (6a,7c), the SCH2 doublet for 2a, n ≥ 6 (in CDCl3; insoluble
in EtOH, which dissolves 2a, n ≤ 8), also appears at δ 3.63, limiting the utility of 1H NMR for
analysis of higher polysulfanes (see Supporting Information for spectra).
The usual LC-MS technique using electrospray ionization mass spectrometry (MS) does not
work with polysulfanes because the sulfane sulfurs are very weak bases and therefore do not

Journal of Sulfur Chemistry 57
undergo protonation. We find that UPLC-(Ag+)CIS-MS is particularly appropriate for product
characterization in view of the very mild MS conditions and the high affinity of silver ions for
divalent sulfur. While HPLC-(Ag+)CIS-MS has proven useful, for example, for analysis of non-
polar and poorly ionized substances such as polyolefins (11a), lipid peroxidation products (11b),
and glycosides (11c), application of this powerful technique to organosulfur compounds has
been very limited (12). Ultra-performance liquid chromatography (UPLC) has an advantage over
HPLC in significantly reducing the elution times with a resultant sharpening of peaks, important
for MS analysis of late-eluting trace components (13). Through the use of UPLC, the 3 h HPLC
separationtimefor 2a wasreducedto∼20 min.TheCIS-MStotalionchromatogram(TIC)showed
2a, n = 2–16. Each polysulfane has isotopic molecular ions for the silver complexes whose
ratios are in excellent agreement with those calculated for 107Ag/109Ag/32S/34S (Figure 3) (14).
Higher polysulfanes 2a (by preparative-HPLC) are stable in MeOH–H2O in the dark and can be
characterized by NMR (Supporting Information); storage at –78◦C prevents disproportionation
into mixtures of higher and lower polysulfanes found with light at 25◦C.
We examined the effect of changing the 1a:S8 ratio and the temperature and found the reaction
to be fastest using a 1:1 molar ratio (8:1, 4:1, 2:1 and 1:1 ratios required 18, 8, 2, and 1 h,
respectively, at 120◦C; very slow at 100◦C and decomposition with red color at 150◦C). We also
examined the reactions of liquid S8 at 120◦C with known disulfides 1b–1f (15), prepared from
commercially available halides. All disulfides except 1f reacted smoothly in high yield giving
families of polysulfanes as shown by HPLC (chains of up to 22 sulfurs), UPLC-(Ag+)CIS-MS
Figure 1. Diallyl disulfide (1a; upper layer) and liquid S8 (lower layer) (left), and homogeneous product diallyl
polysulfane (2a) after 3 min at 120◦C (right).

58 K. Wang et al.
Figure 2. HPLC trace of reaction product of liquid S8 and diallyl polysulfane (2a). The vertical axis corresponds to the
approximate relative abundance of each peak based on UV absorbance. The number of sulfur atoms is listed following
“DAS” in each case.
Figure 3. UPLC-(Ag+)CIS-MS TIC of diallyl polysulfane (2a). Inserts show C6H10S16•Ag+ molecular ion cluster
with Ag and S isotopes. The vertical axis represents the signal intensity, approximating the relative abundance of each
peak.
(chains of up to 15 sulfurs), and 1H NMR spectroscopy. In summary, reaction of 1 with liquid S8
provides a simple route to otherwise unavailable higher diallylic polysulfanes.
From prior work (7c, 16), we suggest (Scheme 2) that thiosulfoxide 3a (17), in equilibrium with
1a, is sufficiently nucleophilic1 (18) to ring-open S8 giving thiosulfonium ion 4a. Nucleophilic

Journal of Sulfur Chemistry 59
transfer of allyl groups between two 4a species could give diallyl decasulfide, one of the major
products seen after only 5 min. Alternatively, 4a could attack S8 prior to allyl transfer giving an
S18 homolog of 4a. Both 4a and its S18 homolog could split out sulfur (Sn) prior to allyl transfer,
giving the observed family of polysulfanes 2a. Further scrambling could occur through nucle-
ophilic attack on 4a by the allyl polysulfane anion formed from mono-deallylation of 4a. Similar
mechanisms can be written involving thiosulfoxides AllS(S)Sn−2All from diallyl polysulfanes;
indeed, diallyl trisulfide 2a, n = 3, as well as 1a reacted with liquid S8. Equilibration of the 2a
mixture by radical processes is also likely. Disulfides 1b–1e can undergo similar processes. After
2 h at 120◦C, 1f failed to react. The unreactivity of 1f is understandable, since the formation of
thiosulfoxide 3f should be disfavored due to the loss of conjugation.
Scheme 2. Proposed mechanism for polysulfane formation involving nucleophilic attack of
thiosulfoxide sulfur on cyclooctasulfur.
To contrast this mechanism with the proposal of Mislow (16b) that both diallyl sulfide and
diallyl disulfide attack S8 in the same manner, without initial involvement of 3a, we followed
by NMR the progress of the reaction of an equimolar mixture of diallyl sulfide and disulfide
with an excess of S8 in the presence of an internal standard. Diallyl disulfide disappears more
than five times faster than the monosulfide, consistent with our favored mechanism, since diallyl
sulfide would be expected to be a stronger S nucleophile than diallyl disulfide (1a) in Mislow’s
mechanism.
The much slower reaction of saturated disulfides with liquid sulfur is also consistent with
our proposal. When dibenzyl disulfide is stirred with liquid S8 under the above conditions, in
contrast to 1a, only 20% reaction occurs after 3 h. Saturated disulfides are presumed to react
with sulfur via free radical processes, with higher activation energies than the processes proposed
for diallyl disulfides. While α-toluenethiol reacts rapidly with liquid S8, giving H2S and dibenzyl
polysulfanes, 2-propenethiolreactswithS8 inthepresenceofcatalyticdiethylamineat50◦Cgiving
a polymer, through addition of sulfur to the double bond, precluding the use of this approach to
polysulfanes 2a (19).
=
GO is a ∼4:1 mixture of 2a and allyl methyl polysulfanes, MeSnCH2CH CH2 (5), and various
minor products including dimethyl polysulfanes, Me2Sn (7). UPLC-(Ag+)CIS-MS analysis of
GO showed it to contain Me2Sn, 2a, n = 3–8, and 5, n = 3–8, as well as families of isomeric
compounds C9H14Sn, n = 2–10 (6, 7), C5H12Sn, n = 2–7 (8a), C7H14Sn, n = 2–8 (8b and 8c)

60 K. Wang et al.
Scheme 3. Formation of silver chelators in liquid sulfur-treated GO.
Figure 4. UPLC-(Ag+)CIS-MSTIC of diallyl polysulfane (2a) in GO before (2a, n = 3–9; left) and after (2a, n = 4–17;
right) liquid S8 treatment. The vertical axis in each trace represents the signal intensity, approximating the relative
abundance of each peak.
and C9H16Sn, n = 2–10 (8d) (Scheme 3). Many of the compounds found are new, although they
were not individually isolated. The enhanced sensitivity seen for 7 and 8 using (Ag+)CIS-MS
compared with the earlier GC–MS studies (7d) reflects the good Ag+ chelating ability of 7 and
8 (Scheme 3, boxes). X-ray structures of Ag+ and Cu(I)+ complexes of 2a, n = 1–4, show that
=
the Group Ia metals coordinate to both S as well as C C (20, 21). However, using synthetic 8a
(m = n = 2), we find (Ag+)CIS-MS to be ∼100 times more sensitive to 8a than 2a (n = 1 or 2).
Individual families of polysulfanes are seen by MS by extracting selected ions (Figures 4 and 5).
The mechanism for the formation of 6–8 follows from our prior work (7d) showing that: (1)
C–S bond cleavage in 1a is energetically favored over S–S bond cleavage. (2) Radical addition,
giving a primary carbon radical (B), is followed by H• abstraction/thioacrolein-forming fragmen-
tation and Diels–Alder addition of thioacrolein giving dihydrothiopyrans 6 and 7 along with the
formation and trapping of thiyl radical Bꢀ giving 8. The alternative process, radical addition giving

Journal of Sulfur Chemistry 61
Figure 5. UPLC-(Ag+)CIS-MS TIC of GO components. C5H12Sn polysulfanes 8a, n = 2–7 (left) and C9H16Sn poly-
sulfanes 8d, n = 2–10 (right) (x + y = n; different x, y combinations for the same value of n result in multiple or split
peaks). The vertical axis represents signal intensity, approximating the relative abundance of each peak.
a secondary carbon radical (A), followed by H• abstraction/thioacrolein-forming fragmentation
and the Diels–Alder formation of 6, 7 as above, along with the formation and trapping of thiyl
radical Aꢀ giving 9, is clearly much less favorable, given that only trace amounts of 9 are found.
(3) The process is completed by scrambling of the R/Rꢀ groups (methyl or allyl) and the number
of sulfur atoms in each separate chain. The presence in GO of 8, previously demonstrated by
GC–MS through comparison with authentic standards, also follows from the presence of charac-
teristic 1H NMR methyl group doublets from 1.34 (8, m = n = 1) to 1.37 ppm (8, m = n = 2) as
well as 13C NMR methyl signals in the expected region (7c) for 8. When liquid sulfur and GO
were kept at 120◦C for 30 min, UPLC-(Ag+)CIS-MS showed that, while families of higher poly-
sulfanes 2a, n = 3–17 (Figure 4), and 5, n = 6–14, were formed, other families of compounds
lacking allyl groups, or having isolated allyl groups, such as Me2Sn and 6–8, were unchanged, or
diminished in concentration. Notably, allyl methyl sulfur also reacted giving polysulfanes with
up to 14 contiguous sulfur atoms.
Our polysulfane synthesis is attractive in that it is fast and solvent free and, for 1a and GO,
uses only naturally occurring materials, in atom-economical one-step, one-pot processes, well
suited for scale-up. Our method is tolerant of functionality, providing access to new materials of
varying solubility and other properties. The higher polysulfanes, now very easily synthesized by
our route, should show very interesting biological activity by analogy to that of the well-studied 2a,
n = 2–5 (8). As demonstrated by our work with GO, UPLC-(Ag+)CIS-MS represents a powerful
technique for analysis of complex mixtures of non-polar sulfur compounds, particularly those
with multiple sulfur atoms which can chelate silver (or other metal ions). Finally, in view of the
natural occurrence of liquid sulfur in proximity to thermophilic microorganisms, it would be of
interest to search for sulfur-rich natural products formed by the processes described here.
3. Experimental
3.1. General
Reagents were obtained from commercial sources and used without further purification. Dry
diethyl ether and THF were distilled from sodium–benzophenone under argon. All other dried
solvents were obtained by storage over 3 or 4Å molecular sieves overnight. 1H (400 MHz) and 13
C
(100.5 MHz) NMR spectra were obtained on a Bruker Avance 400 NMR spectrometer. Chemical
shifts were referenced to residual 1H and 13C signals of the deuterated chloroform (1H 7.26 ppm
and 13C 77.36 ppm). UV–VIS spectra were obtained on a Varian Prostar 330 photodiode array

62 K. Wang et al.
detector. Analytical TLC was performed on Merck silica gel 60 F254 TLC plates and visualized
by UV or I2/silica. Flash chromatography was carried out with Adedge 32-63 D 60Å silica
gel. Analytical HPLC analysis was performed on Varian Prostar 210 with Microsorb-MV 100-5
C18 250 × 4.6 mm column and Varian Prostar 330 photodiode array detector. Preparative HPLC
isolations were performed onVarian Prostar 218 with Rainin Dynamax® 60Å C18 250 × 21.4 mm
column and Varian Prostar 325 UV–VIS detector. UPLC-(Ag+)CIS-MS analysis was carried
out by Dr. Robert Sheridan on a Waters Acquity UPLC with Waters Quattro Premier XE triple
quadrupole mass spectrometer. Detailed UPLC-(Ag+)CIS-MS data for the various polysulfane
mixtures is provided in the Supporting Information.
3.2. Bis-(2-propenyl) polysulfane mixture (2a)
Cautionary note: when working on a much larger scale than described below (e.g. ≥ 100 larger),
it is important to avoid heating significantly above 120◦C by providing quick removal of the
heating source as well as external cooling as needed, together with adequate stirring. Overheating
can result in an exothermic reaction with darkening and gas evolution. A 10 ml round-bottomed
flask containing sublimed sulfur (S8, 0.640 g, 2.50 mmol) was placed in an oil bath pre-heated
to 120◦C. When all of the sulfur had melted into a clear, straw-colored liquid, 1a (0.365 g,
2.50 mmol) was added all at once to the magnetically stirred liquid (1.1:1 S8:1a ratio). Within
3 min, the initial cloudy two-layer liquid mixture became clear and homogeneous. Samples were
withdrawn for analysis at 5 min, 30 min, 1 h, 1.5 h, and 2 h. These samples were dissolved in
CDCl3 permitting both NMR and reversed phase HPLC analysis to be performed simultaneously.
HPLC traces are given in the Supporting Information. For the 30 min sample, disulfide 1a eluted at
3.8 min, S8 eluted between theheptasulfideand octasulfideat23.8 min, andthehighestpolysulfane
seen, eluting at 149 min, had a chain of 21 sulfur atoms. Similar results were obtained using
diallyl trisulfide instead of 1a. When the reaction of 1a and S8 is sampled after 1 h, less sulfur
remains and the strongest polysulfane peak shifts to a higher number of sulfur atoms than for
the 30 min sample. Individual pure polysulfanes can be isolated by preparative HPLC (85:15
MeOH:H2O) on a reversed phase column, with concentration under reduced pressure, extraction
into pentane, drying (Na2SO4), and re-concentration. Higher polysulfanes, for example, diallyl
hexasulfide, are sensitive to light and traces of ammonia or amines and should be refrigerated.
1
Purity after preparative HPLC was established by analytical HPLC as well as by H NMR, as
illustrated for diallyl trisulfide (2a, n = 3) and diallyl hexasulfide (2a, n = 6), as representative
+
1
examples (see Supporting Information for H NMR spectra and UPLC-(Ag )CIS-MS data).
Ethanol and methanol only partially dissolved 2a. The soluble and insoluble portions of 2a in
EtOH and MeOH, after concentration, were separately redissolved in CDCl3 and analyzed (1H
NMR). In MeOH/EtOH insoluble portions, only one δ 3.64 doublet signal corresponding to SCH2
for 2a (n > 5) appeared, whereas in MeOH/EtOH soluble portions, four doublets δ 3.10–3.62
corresponding to SCH2 for 2a (n = 2, 3, 4, 5) appeared. A smaller δ 3.64 doublet (SCH2 for 2a,
n ≥ 5) was found in the soluble portion in MeOH compared with EtOH, suggesting that higher
polysulfanes 2a (n ≥ 5) have less solubility in MeOH than in EtOH.
3.3. Ethanethioic acid, S-(2-methyl-2-propenyl) ester
Potassium thioacetate (2.50 g, 22 mmol) was added to a solution of 3-chloro-2-methylprop-1-ene
(1.81 g, 20 mmol) in THF (50 ml). The mixture was stirred overnight giving an orange-yellow
solution with a colorless precipitate. The solution was passed through a silica gel pad and then
concentrated in vacuo to give a yellow oil (1.50 g, 58%) which was directly used for the next step;
1H NMR (400 MHz, CDCl3) δ 1.73 (s, 3H), 2.32 (s, 3H ), 3.52 (s, 2H ), 4.81 (s, 1H), 4.92 (s, 1H);
13C NMR δ 21.16, 30.43, 35.98, 114.00, 140.73, 195.24 ppm.

Journal of Sulfur Chemistry 63
3.4. Bis-(2-methyl-2-propenyl) disulfide (1b)
Sodium chips (0.24 g, 10.0 mmol) were added to dry MeOH (50 ml) at 0◦C. The mixture was
stirred until the sodium was consumed. Ethanethioic acid, S-(2-methyl-2-propenyl) ester (1.30 g,
10.0 mmol) was added to the above solution at 0◦C followed by I2 (1.26 g, 5.0 mmol) after 2 h.
The mixture was stirred for 30 min and then concentrated and purified by silica gel column
1
chromatography (hexane) giving the known (22) 1b as a light yellow liquid (0.68 g, 67%); H
NMR (400 MHz, CDCl3) δ 1.81 (s, 6H), 3.27 (s, 4H), 4.87 (s, 2H), 4.90 (s, 2H); 13C NMR δ
20.83, 46.45, 114.93, 140.72 ppm.
3.5. Bis-(2-methyl-2-propenyl) polysulfane mixture (2b)
See above cautionary note for 2a. Sublimed sulfur (S8, 0.640 g, 2.50 mmol) was liquefied as for 2a.
When all of the sulfur had melted, a solution of 4, 4ꢀ-di-tert-butylbiphenyl (0.0308 g, 0.116 mmol)
in 1b (0.415 g, 2.38 mmol) was added all at once to the magnetically stirred liquid (1.1:1 S8:1b
ratio). Within 3 min, the initial cloudy two-layer liquid mixture became a clear and homogeneous
solution with a single liquid layer. Samples were withdrawn for NMR/HPLC analysis at intervals
as for 2a (see Supporting Information for HPLC and UPLC-(Ag+)CIS-MS data). For the 30 min
sample, disulfide 1b eluted at 6 min, S8 eluted at 24 min overlapping with the hexasulfide, the
internal standard eluted at 37.5 min, and the highest polysulfane seen, eluting at 179 min, had a
chain of 21 sulfur atoms.
3.6. Ethanethioic acid, S-(2-chloro-2-propenyl) ester
Potassium thioacetate (2.50 g, 22 mmol) was added to a solution of 3-chloro-2-chloroprop-1-ene
(2.22 g, 1.83 ml, 20 mmol) in THF (50 ml). The mixture was stirred overnight to give an orange
yellow solution with white precipitate. Workup as above gave a red liquid (2.31 g, 77% yield),
used for the next step: 1H NMR (400 MHz, CDCl3) δ 2.37(s, 3H), 3.78 (s, 2H), 5.25 (s, 1H), 5.42
(s, 1H); 13C NMR δ 30.35, 36.81, 115.16, 137.45, 193.84 ppm.
3.7. Bis-(2-chloro-2-propenyl) disulfide (1c)
As for 1b, to NaOMe from Na (0.24 g, 10.0 mmol) and MeOH (50 ml), ethanethioic acid, S-(2-
chloro-2-propenyl) ester (1.50 g, 10.0 mmol) was added at 0◦C followed by I2 (1.26 g, 5.0 mmol).
1
Workup gave the known (23) 1c as a light yellow liquid (0.81 g, 75%); H NMR (400 MHz,
CDCl3) δ 3.52 (s, 4H), 5.31 (s, 2H), 5.42 (s, 2H); 13C NMR δ 47.27, 116.39, 137.37 ppm.
3.8. Bis-(2-chloro-2-propenyl) polysulfane mixture (2c)
See above cautionary note for 2a. Sublimed sulfur (S8, 0.256 g, 1.0 mmol) was liquefied as for
2a. When the sulfur had melted, 1c (0.215 g, 1.0 mmol) was added. Within 3 min the initial two-
layer liquid mixture became clear and homogeneous. Samples were withdrawn for NMR/HPLC
analysis at intervals as for 2a (see Supporting Information for HPLC and UPLC-(Ag+)CIS-MS
data). For the 30 min sample, disulfide 1c eluted at 4 min, S8 eluted between the heptasulfide and
octasulfide at 23.7 min, and the highest polysulfane seen, eluting at 159 min, had a chain of 23
sulfur atoms.

64 K. Wang et al.
3.9. Ethanethioic acid, S-(3-methyl-2-butenyl) ester
Potassium thioacetate (2.50 g, 22 mmol) was added to a solution of 1-bromo-3-methylbut-2-ene
(2.98 g, 2.33 ml, 20 mmol) in THF (50 ml). After overnight stirring, workup gave a yellow oil
(2.86 g, 99%), used for the next step; 1H NMR (400 MHz, CDCl3) δ 1.66 (s, 3H), 1.69 (s, 3H),
2.29 (s, 3H), 3.49, 3.51 (d, 2H), 5.18 (t, 1H); 13C NMR δ 17.75, 25.61, 27.39, 30.41, 118.60,
136.59, 196.04 ppm.
3.10. Bis-(3-methyl-2-buten-1-yl) disulfide (1d)
As for 1b, to NaOMe from Na (0.12 g, 5.0 mmol) and MeOH (25 ml) at 0◦C, ethanethioic acid,
S-(3-methyl-2-butenyl) ester (0.72 g, 5.0 mmol) was added to the above solution at 0◦C followed
by I2 (0.63 g, 2.50 mmol). Workup gave the known (23) 1d as a light yellow liquid (0.36 g, 71%);
1H NMR (400 MHz, CDCl3) δ 1.69 (s, 6H), 1.76 (s, 6H), 3.37, 3.39 (d, 4H), 5.27 (t, 2H); 13C
NMR (CDCl3) δ 17.94, 25.80, 37.58, 119.44, 137.14 ppm.
3.11. Bis-(3-methyl-2-buten-1-yl) polysulfane mixture (2d)
See above cautionary note for 2a. Sublimed sulfur (S8, 0.256 g, 1.0 mmol) was liquefied as for 2a.
When the sulfur had melted, 1d (0.202 g, 1.0 mmol) was added. After 35 min, the initial two-layer
liquid mixture turned red and became homogeneous. Samples were withdrawn for NMR/HPLC
analysis at intervals as for 2a (see Supporting Information for HPLC and UPLC-(Ag+)CIS-MS
data). For the 6 h sample, disulfide 1d eluted at 9.4 min, S8 eluted between the tetrasulfide and
pentasulfide at 22.7 min, and the highest polysulfane seen, eluting at 187 min, had a chain of 20
sulfur atoms.
3.12. Ethanethioic acid, S-2-cyclohexen-1-yl ester
Potassium thioacetate (1.25 g, 11 mmol) was added to a solution of 3-bromocyclohex-1-ene
(1.61 g, 10.0 mmol) in THF (25 ml). The mixture was stirred overnight to give a brown solu-
tion with white precipitate. Workup as above gave the known (24) title compound as a brown
liquid (1.35 g, 87% yield), used for the next step; 1H NMR (400 MHz, CDCl3) δ 1.64–2.02 (m,
6H), 2.28 (s, 3H), 3.72 (m, 1H), 5.60 (m, 1H), 5.80 (m, 1H); 13C NMR δ 19.97, 24.64, 29.48,
30.45, 39.82, 126.14, 130.78, 195.72 ppm.
3.13. Bis-(2-cyclohexen-1-yl) disulfide (1e)
As for 1b, to NaOMe from Na (0.12 g, 5.0 mmol) and MeOH (25 ml) at 0◦C, ethanethioic acid,
S-2-cyclohexen-1-yl ester (0.78 g, 5.0 mmol) was added at 0◦C followed by I2 (0.63 g, 2.5 mmol).
1
Workup gave the known (23) 1e as a light yellow liquid (0.44 g, 78%); H NMR (400 MHz,
CDCl3) δ 1.78–1.99 (m,12H), 3.47–3.51 (m, 2H), 5.72 (m, 2H), 5.84 (m, 2H); 13C NMR δ 18.86,
25.14, 28.31, 47.98, 126.30, 131.39 ppm.
3.14. Bis-(2-cyclohexen-1-yl) polysulfane mixture (2e)
See above cautionary note for 2a. Sublimed sulfur (S8, 0.256 g, 1.0 mmol) was liquefied as for 2a.
When the sulfur had melted, 1e (0.226 g, 1.0 mmol) was added. Within 3 min, the initial two-layer
liquid mixture became a clear, homogeneous solution. Samples were withdrawn for NMR/HPLC
analysis at intervals as for 2a (see Supporting Information for HPLC and UPLC-(Ag+)CIS-MS

Journal of Sulfur Chemistry 65
data). For the 2 h run, disulfide 1e eluted at 14.5 min, S8 overlapped with the trisulfide at 23.7 min,
and the highest polysulfane seen, eluting at 226 min, had a chain of 19 sulfur atoms.
3.15. 1,2-Bis(methylthio)propane (8a)
Sodium metal (0.46 g, 10 mmol) was added to MeOH (10 ml) at 0◦C. After the Na disappeared,
1,2-propanedithiol (1.0 g, 9 mmol) was added and the mixture was stirred at rt for 1 h. Methyl
iodide (2.84 g, 10 mmol) was added and the mixture was refluxed for 2 h. Water was added and the
mixture was extracted with pentane. The combined, dried (Na2SO4) extracts were concentrated
1
in vacuo, giving the known (25) 8a as a colorless oil (1.13 g, 93% yield); H NMR (400 MHz,
CDCl3) δ 1.35 (d, J = 6.6 Hz, 3H), 2.10 (s, 3H), 2.12 (s, 3H), 2.53 (m, 1H), 2.81 (m, 2H).
Acknowledgements
This work was supported by the National Science Foundation (CHE-0342660, CHE-0450505, and CHE-0744578). Initial
phases of this research were performed by E.B. and M.G. at the UK laboratories of ECOspray Ltd; E.B. thanks ECOspray
for hosting his visits in the UK. Queries regarding GO-based pesticides should be directed to M.G.: groom@ecospray.com.
Supporting Information
NMR and UV spectra, HPLC, UPLC-(Ag+)CIS-MS TIC andAg-complex data for 1a–1e and 2a–2e and GO components
are provided as Supporting Information.
Note
=
1. Thiosulfoxides are typically drawn with an S S double bond (17), but the π-bond is calculated to be polarized,
with the terminal sulfur being negatively charged (18), and capable of functioning as a nucleophile (7d).
References
(1) Oppenheimer, C.; Stevenson, D. Nature 1989, 342, 790–793.
(2) Steudel, R. Top. Curr. Chem. 2003, 230, 81–116.
(3) Chung, W.J.; Simmonds, A.G.; Griebel, J.J.; Kim, E.T.; Suh, H.S.; Shim, I.; Glass, R.S.; Loy, D.A.; Theato, P.; Sung,
Y. Angew. Chem., Int. Ed. 2011, 50, 11409–11412.
(4) Zhang, J.; Zhang, M.; Zhang, G.; Wang, X. ACS Catal. 2012, 2, 940−948.
(5) Steudel, R. Chem. Rev. 2002, 102, 3905–3945.
(6) (a) Grant, D.; Van Wazer, J.R. J. Am. Chem. Soc. 1964, 86, 3012–3017. (b) Langer, H.J.; Hyne, J.B. Adv. Chem. Ser.
1972, 110, 113–129. (c) Bisseret, P.; Rohmer, M. Tetrahedron Lett. 1990, 31, 7445–7448. (d) Bisseret, P.; Rohmer,
M. Tetrahedron Lett. 1993, 34, 5295–5298.
(7) (a) Groom, M.; Block, E. US Patent 8,101,802 B2, 1/24/2012. (b) Block, E. Garlic and Other Alliums: The Lore
and the Science; Royal Society of Chemistry: Cambridge, 2010. (c) Hile, A.G.; Shan, Z.; Zhang, S.-Z.; Block, E.
J. Agric. Food Chem. 2004, 52, 2192–2196. (d) Block, E.; Iyer, R.; Grisoni, S.; Saha, C.; Belman, S.; Lossing, F.P.
J. Am. Chem. Soc. 1988, 110, 7813–7827.
(8) (a) Montenarh, M.; Saidu, N.E. Nat. Prod. Commun. 2012, 7, 401–408. (b) Ponnusamy, M.; Pari, L. Toxicol. Ind.
Health 2011, 27, 407–416. (c) Viry, E.; Anwar, A.; Kirsch, G.; Jacob, C.; Diederich, M.; Bagrel, D. Int. J. Oncol.
2011, 38, 1103–1111. (d) Nishida, M.; Hada, T.; Kuramochi, K.;Yoshida, H.;Yonezawa,Y.; Kuriyama, I.; Sugawara,
F.; Yoshida, H.; Mizushina, Y. Food Chem. 2008, 108, 551–560. (e) Münchberg, U.; Anwar, A.; Mecklenburg, S.;
Jacob, C. Org. Biomol. Chem. 2007, 5, 1505–1518. (f) Hosono, T.; Fukao, T.; Ogihara, J.; Ito,Y.; Shiba, H.; Seki, T.
J. Biol. Chem. 2005, 280, 41487–41493. (g) Wu, C.C.; Chung, J.G.; Tsai, S.J.; Yang, J.H.; Sheen, L.Y. Food Chem.
Toxicol. 2004, 42, 1937–1947.
(9) (a) Arisawa, M.; Tanaka, K.;Yamguchi, M. Tetrahedron Lett. 2005, 46, 4797–4800; (b) Kamyshny, A., Jr.; Goifman,
A.; Gun, J.; Rizkov, D.; Lev, O. Environ. Sci. Technol. 2004, 38, 6633–6644; (c) Barany, G.; Mott, A.W. J. Org.
Chem. 1984, 49, 1043–1051.
(10) Steudel, R.; Hassenberg, K.; Münchow, V.; Schumann, O.; Pickardt, J. Eur. J. Inorg. Chem. 2000, 921–928.

66 K. Wang et al.
(11) (a) Bayer, E.; Gfrorer, P.; Rentel, C. Angew. Chem., Int. Ed. 1999, 38, 992–995. (b) Havrilla, C.M.; Hachey, D.L.;
Porter, N.A. J. Am. Chem. Soc. 2000, 122, 8042–8055. (c) Zhang, J.; Brodbelt, J.S. Anal. Chem. 2005, 77, 1761–1770.
(d) Johnson, B.S.; Burinsky, D.J.; Burova, S.A.; Davis, R.; Fitzgerald, R.N.; Matsuoka, R.T. Rapid Commun. Mass
Spectrom. 2012, 26, 1115–1122.
(12) (a) Hayen, H.; Alvarez-Grima, M.M.; Debnath, S.C.; Noordermeer, J.W.M.; Karst, U. Anal. Chem. 2004, 76,
1063–1068. (b) Li, L.; Yang, H.; Chen, X.; Xu, L. Fenxi Huaxue 2006, 34, 1183–1186; Chem. Abstr. 2006, 146,
1216171. (c) Chen, H.; Wortmann, A.; Zhang, W.; Zenobi, R. Angew. Chem., Int. Ed. 2007, 46, 580–583.
(13) (a) Swartz, M. Sep. Sci. Technol. 2007, 8, 145–187. (b) Novakova, L.; Matysova, L.; Solich, P. Talanta 2006, 68,
908–918. (c) Churchwell, M.I.; Twaddle, N.C.; Meeker, L.R.; Doerge, D.R.J. Chromatogr. B. 2005, 825, 134–143.
(14) Isotope ratios. http://www.colby.edu/chemistry/NMR/IsoClus.html (accessed August 13, 2012).
(15) 1b: Yamada, N.; Furukawa, M.; Nishi, M.; Takata, T. Chem. Lett. 2002, No. 4, 454–455. 1c: Segall, Y.; Casida, J.E.
J. Agric. Food Chem. 1983, 31, 242–246. 1d and 1e: Moore, C.G.; Trego, B.T. Tetrahedron 1962, 18, 205–218. 1f:
Sinha, S.; Ilankumaran, P.; Chandrasekaran, S. Tetrahedron 1999, 55, 14769–14776.
(16) (a) Höfle, G.; Baldwin, J.E. J. Am. Chem. Soc. 1971, 93, 6307–6308. (b) Baechler, R.B.; Hummel, J.P.; Mislow, K.
J. Am. Chem. Soc. 1973, 95, 4442–4444.
(17) Kutney, G.W.; Turnbull, K. Chem. Rev. 1982, 82, 333–357.
(18) Miaskiewicz, K.; Steudel, R. J. Chem. Soc. Dalton Trans. 1991, 2395–2399.
(19) Bordoloi, B.K.; Pearce, E.M. J. Polymer Sci., Polymer Chem. Ed. 1978, 16, 3293–3300.
(20) (a) Salivon, N.F.; Oliinik, V.V. Russ. J. Coord. Chem. 2006, 32, 208–213. (b) Salivon, N.F.; Filinchuk,Y.E.; Olijnyk,
V.V.Z. Anorg. Allg. Chem. 2006, 632, 1610–1613.
(21) Salivon, N.F.; Olijnik, V.V.; Shkurenko, A.A. Russ. J. Coord. Chem. 2007, 33, 908–913 and references therein.
(22) Segall, Y.; Casida, J.E. J. Agric. Food Chem. 1983, 31, 242–246.
(23) Moore, C.G.; Trego, B.T. Tetrahedron 1962, 18, 205–218.
(24) (a) Divekar, S.; Safi, M.; Soufiaoui, M.; Sinou, D. Tetrahedron 1999, 55, 4369–4376; (b) Luessem, B.J.; Gais, H.-J.
J. Org. Chem. 2004, 69, 4041–4042.
(25) Sugawara, A.; Ishiyama, M.; Abe, Y.; Segawa, T.; Sato, R. Sulfur Lett. 1990, 12, 55–60.